Tag: bone fractures

Nick Evans and his colleagues at the University of Southampton, UK have discovered that transient stimulation of the Wnt signaling pathway in bone marrow stem cells expands them and enhances their bone-making ability. This finding has led to an intense search for drugs that can stimulate the Wnt pathway in order to stimulate bone formation in wounded patients.

The Wnt pathway is a highly conserved pathway found in sponges, starfish, sharks, and people. Wnt signaling controls pattern formation during development, and the growth of stem cells during healing.

When it comes to healing, bone fractures represent a sizeable societal problem, particularly among the aged. While most fractures heal on their own, approximately 10 percent of all fractures take over six months to heal or never heal at all. In the worse cases, fracture patients can require several surgeries or might need amputation in desperate cases.

According the Evans, he and his research group are screening a wide range of chemicals to determine if they stimulate Wnt signaling. If such chemicals prove safe to use in laboratory animals, then they might become clinical tools to help stimulate bone formation and healing in patients with recalcitrant fractures.

Research from Evans’ group has shown that transient stimulation of the Wnt signaling pathway in isolated bone marrow cells increases the number of bone-making progenitor cells. However, if the Wnt pathway is activated for too long a time period, this regenerative effect is lost or even reversed. Hence the need to develop treatments that deliver small molecules that stimulate Wnt signaling in bone marrow cells for a specified period of time and in a targeted fashion.

Evans and his group have used nanoparticles loaded with Wnt proteins to do exactly that. The feasibility of this technology and its effectiveness requires further work, but the promise is there and the idea is more than a little intriguing.

Clive Randell loves motorcycles, but an unfortunate accident in 2011 seriously injured his leg and potentially prevented him from ever riding his beloved Harley-Davidson motorcycle again. His leg had several open fractures and one particular fracture that left some bone that protruded through his skin. He had extensive skin loss, and his doctors told me several times that his leg would have to be amputated. Things looked grim to say the least.

However, new stem cell procedure that repairs severely fractured bones has healed his bad leg and saved Clive from amputation. In fact, now Clive can ride his motorbike again. This new, pioneering stem cell procedure could give a new hope for victims of severe accidents who face limb amputation.

This new procedure uses stem cells extracted from the patient’s bone marrow from the patient’s pelvis and then mixes these cells with a specially created gel matrix to provide the cells with the right environment in order for them to form bone. This stem cell/matrix was then injected into the damaged bone with some hardware, such as a rod, which is inserted into the bone for support. Over time, the stem cells regenerate bone at the fracture site, traversing the fracture with new bone and completely healing the damaged bone.

The intrepid physician who used this new procedure to heal Mr. Randall is Professor Anan Shetty, who serves as the Deputy Director of Minimally Invasive Surgery at Kent’s Canterbury Christ Church University. The motivation behind Dr. Shetty’s research is easy to understand. In the United Kingdom alone there are 350,000 serious fractures every year. Five to ten percent of these fractures are too extensive to heal and demand multiple surgeries, bone grafts, and other procedures that sometimes end in limb amputation if they fail to produce satisfactory results.

The fractured bone lacks an established blood supply, which means that it is very tough going for any implanted stem cells. Implanted stem cells have no way to receive signals to regenerate damaged cells. This new treatment circumvents this problem by using the bioengineered gel that contains the ingredients to that tells the stem cells what to do.

According to Professor Shetty, “Experiments have shown that collagen [gels] can trigger the transformation of stem cells into bone forming cells.” Dr. Shetty continued: “These “miracle” cells are abundant in bone marrow, so may be harvested, concentrated and applied with a collagen ‘scaffold’ into an area of poor healing.”

According to Clive Randall, “I may never dance the tango, but, thanks to Professor Shetty, I will be able to get as near to normal as possible.”

This bone-healing operation is performed under a general anaesthesia and only takes 30 minutes, after which the patient can walk out of the hospital and go home on the same day as the procedure. To date, six patients in the UK, four in India and 20 in South Korea have undergone this procedure.

Bone marrow for this procedure is drawn from the crest of the ilium of the patient’s pelvis by means of a stiff, hollow needle. Bone marrow contains a mixture of differ types of stem cells (including hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells), and red blood cells. The bone marrow extract is then concentrated through centrifugation, but the red blood cells are usually removed. The concentrated bone marrow stem cell preparation is then mixed with collagen and this mixture is ready for implantation by injection.

For the surgical procedure, the surgeon stabilizes the fracture with a plate or long metal rod that is inserted through the central medullary canal or the bone. These stabilizing tools can be inserted with a small incision. The stem cell and collagen suspension is then injected into the fracture site and around the bone, guided by either live fluoroscopy or X-ray.

After the surgery, the patient is actually allowed put some weight on the affected limb, and is instructed to progressively increase the load he or she applies through his leg. Interestingly, Prof Shetty’s pioneering procedure cuts the healing time associated with these types of procedures in half, and at a cost of about $3,500 to $5,200, costs a fraction of the hundreds of thousands of dollars usually involved in amputation, rehabilitation and fitting the patient for prosthetics.

Professor Norimasa Nakamura, president elect of the International Cartilage Repair Society and one of the world’s leading authorities on stem cell treatment, has welcomed Prof Shetty’s work, saying: “It will revolutionize the whole field of bone fracture repairs. The patient has a more effective treatment and the health provider saves money. It’s a win-win situation.”

After his accident, Clive Randall, who worked as a high-altitude window cleaner who lived in Orpington, Kent, had a cage screwed to his damaged leg. He also underwent three bone grafts and several other procedures within 18 months after his accident. The accident also drastically changed his life. Even though the driver of the car was successfully prosecuted, he lost his job, girlfriend, and most of his money. He also had to take a deal of pain medication and became greatly depresses; at one time, understandably, he contemplated suicide. In a kind of “Hail Mary,” Clive turned to the internet and typed “I want to save my leg.”

He found Prof Shetty’s name, and the rest is history, but he is still in a state of disbelief over the reversal in his fortunes since having the operation in 2012. He said, “Six hours after the operation, Professor Shetty told me to get up and go for a walk. After being in and out of hospitals, I really couldn’t believe it. I’d suffered 15 months of being told there was a good chance I was going to lose my leg, yet eight weeks after the procedure I was told to start putting weight on it and to walk as much as I could. It still hurts to walk long distances, but that will improve. My foot is turned out a little bit to the side and I have a limp, but that’s a small price to pay to keep my leg. My hope is this procedure will eventually be available to everyone, since it can help so many people, particularly the military. The old way of mending broken bones is so painful and stops you getting on with your life. Professor Shetty’s stem cell surgery is quick and almost painless, so it’s important more people hear about it.”

There you have it from the patient himself. Now only if the power-hungry, control-driven FDA would get off their duffs and look into bringing this procedure to the US?